Orally disintegrating tablets (ODT) have become a preferred dosage form for delivering active agents to patients having difficulty swallowing or who experience dysphagia. These patients generally have trouble swallowing large tablets or capsules and may experience reduced compliance to recommended dosing regimens. Thus, these ODT compositions which rapidly disintegrate in the oral cavity provide minimum patient discomfort.
ODTs are typically produced as a single unit form or a multiunit system in which a plurality of particles, each containing an active ingredient, are compressed into a single dosage form. Generally, multiunit systems are preferred for several reasons. For example, following disintegration of the tablet, the plurality of particles distribute over a large area thereby preventing high concentrations of a drug in one location. Further, multiunit systems have a decreased transit time variance, predictable gastric emptying, less absorption variability, and decreased dose dumping risks.
Despite these benefits, the methods for manufacturing ODTs as multiunit system can result in tablets, which are soft, friable, and unsuitable for packaging in typical blister packs or bottles. Thus, designing ODTs as multiunit system, which are stable during manufacturing and storage and also have acceptable friability, remains a challenge.
Additionally, many active pharmaceutical ingredients are susceptible to highly acidic environments. For example, proton pump inhibitors which most commonly are benzimidazole derivatives are susceptible to degradation and transformation in acidic media. These types of active ingredients should be protected both during storage and during their passage through the acidic environment of the stomach. Therefore, multiunit ODTs having acid-labile active pharmaceutical ingredients are typically formulated with enteric coatings, which are applied to the particles. However, stability problems can arise when particles coated with enteric coatings are compressed into a tablet. Typically, enteric coatings suffer from increased brittleness, which causes cracking during the compression tableting process. Plasticizers can aid in reducing cracking of the coatings, however, when used in excess, they may decrease the effectiveness of the enteric coat.
There have been known approaches to formulate and manufacture ODTs see, for example Fu, Y. Orally Fast Disintegrating Tablets: Developments, Technologies, Taste masking and Clinical Studies. Critical Reviews™ in Therapeutic Drug Carrier Systems. 21, 433-475. Many of these approaches are characterized by several advantages including quick disintegration in the oral cavity. However, they are most often accompanied by high levels of friability and/or sensitivity to humidity. Alternatively, the hitherto known compositions may be formulated to have increased stability and hardness, but as a result suffer from longer disintegration times. Thus, there remains a need for ODT compositions, which demonstrate fast disintegration times, reduced taste of bitter active ingredients, and high stability (e.g., low friability).